Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908-1355, USA.
Immunol Rev. 2011 Jul;242(1):51-68. doi: 10.1111/j.1600-065X.2011.01021.x.
Allergens are recognized as the proteins that induce immunoglobulin E (IgE) responses in humans. The proteins come from a range of sources and, not surprisingly, have many different biological functions. However, the delivery of allergens to the nose is exclusively on particles, which carry a range of molecules in addition to the protein allergens. These molecules include pathogen-associated molecular patterns (PAMPs) that can alter the response. Although the response to allergens is characterized by IgE antibodies, it also includes other isotypes (IgG, IgA, and IgG4), as well as T cells. The challenge is to identify the characteristics of these exposures that favor the production of this form of response. The primary features of the exposure appear to be the delivery in particles, such as pollen grains or mite feces, containing both proteins and PAMPs, but with overall low dose. Within this model, there is a simple direct relationship between the dose of exposure to mite or grass pollen and the prevalence of IgE responses. By contrast, the highest levels of exposure to cat allergen are associated with a lower prevalence of IgE responses. Although the detailed mechanisms for this phenomenon are not clear, it appears that enhanced production of interleukin-10 in response to specific Fel d 1 peptides could influence the response. However, it is striking that the animal sources that are most clearly associated with decreased responses at high allergen dose are derived from animals from which humans evolved more recently (∼65 million years ago). Although the nose is still recognized as the primary route for sensitization to inhalant allergens, there is increasing evidence that the skin is also an important site for the generation of IgE antibody responses. By contrast, it is now evident that delivery of foreign proteins by the oral route or sublingually will favor the generation of tolerance.
过敏原被认为是能在人体中诱导免疫球蛋白 E（IgE）反应的蛋白质。这些蛋白质来自于多种来源，具有许多不同的生物学功能，这并不奇怪。然而，过敏原被递送到鼻子里的途径仅存在于颗粒中，这些颗粒除了携带蛋白质过敏原之外，还携带了一系列分子。这些分子包括可以改变反应的病原体相关分子模式（PAMPs）。尽管对过敏原的反应以 IgE 抗体为特征，但它也包括其他同种型（IgG、IgA 和 IgG4）以及 T 细胞。挑战在于确定有利于产生这种形式反应的这些暴露的特征。暴露的主要特征似乎是在颗粒中递呈，例如花粉粒或螨虫粪便，其中既包含蛋白质也包含 PAMPs，但总体剂量较低。在这种模式下，暴露于螨虫或草花粉的剂量与 IgE 反应的普遍性之间存在简单的直接关系。相比之下，接触猫过敏原的最高水平与较低的 IgE 反应流行率相关。尽管这种现象的详细机制尚不清楚，但似乎是对特定 Fel d 1 肽的反应增强产生了白细胞介素-10，从而影响了反应。然而，令人惊讶的是，与高过敏原剂量下反应降低最明显相关的动物来源是来自于人类最近进化而来的动物（约 6500 万年前）。尽管鼻子仍然被认为是对吸入性过敏原致敏的主要途径，但越来越多的证据表明皮肤也是产生 IgE 抗体反应的重要部位。相比之下，现在已经很明显，通过口服或舌下途径递呈外来蛋白质会有利于产生耐受性。
